Insulin Directs Dichotomous Translational Regulation to Control Human Pluripotent Stem Cell Survival, Proliferation and Pluripotency

Insulin is essential for diverse biological processes in human pluripotent stem cells (hPSCs). However, the underlying mechanism of insulin's multitasking ability remains largely unknown. Here, we show that insulin controls hPSC survival and proliferation by modulating RNA translation via disti...

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Published in:International journal of biological sciences 2022-01, Vol.18 (9), p.3562-3575
Main Authors: Zhou, Xiaoxiao, Ren, Zhili, Xu, Jiaqi, Deng, Chunhao, Zhang, Zhaoying, Godoy-Parejo, Carlos, Xu, Faxiang, Huang, Esther Chi Cheng, Wang, Jiajia, Cai, Zheyu, Liu, Weiwei, Hu, Guang, Chen, Guokai
Format: Article
Language:English
Subjects:
AKT protein
Apoptosis
Biological activity
Cell growth
Cell proliferation
Cell survival
Gene expression
Initiation factor eIF-4E
Insulin
Kinases
Multitasking
Phosphorylation
Pluripotency
Protein synthesis
Proteins
Rapamycin
Reagents
Research Paper
Ribonucleic acid
RNA
Stem cells
Sucrose
Survival
TOR protein
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container_issue 9
container_start_page 3562
container_title International journal of biological sciences
container_volume 18
creator Zhou, Xiaoxiao
Ren, Zhili
Xu, Jiaqi
Deng, Chunhao
Zhang, Zhaoying
Godoy-Parejo, Carlos
Xu, Faxiang
Huang, Esther Chi Cheng
Wang, Jiajia
Cai, Zheyu
Liu, Weiwei
Hu, Guang
Chen, Guokai
description Insulin is essential for diverse biological processes in human pluripotent stem cells (hPSCs). However, the underlying mechanism of insulin's multitasking ability remains largely unknown. Here, we show that insulin controls hPSC survival and proliferation by modulating RNA translation via distinct pathways. It activates AKT signaling to inhibit RNA translation of pro-apoptotic proteins such as NOXA/PMAIP1, thereby promoting hPSC survival. At the same time, insulin acts via the mTOR pathway to enhance another set of RNA translation for cell proliferation. Consistently, mTOR inhibition by rapamycin results in eIF4E phosphorylation and translational repression. It leads to a dormant state with sustained pluripotency but reduced cell growth. Together, our study uncovered multifaceted regulation by insulin in hPSC survival and proliferation, and highlighted RNA translation as a key step to mediate mitogenic regulation in hPSCs.
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subjects AKT protein
Apoptosis
Biological activity
Cell growth
Cell proliferation
Cell survival
Gene expression
Initiation factor eIF-4E
Insulin
Kinases
Multitasking
Phosphorylation
Pluripotency
Protein synthesis
Proteins
Rapamycin
Reagents
Research Paper
Ribonucleic acid
RNA
Stem cells
Sucrose
Survival
TOR protein
title Insulin Directs Dichotomous Translational Regulation to Control Human Pluripotent Stem Cell Survival, Proliferation and Pluripotency
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